The Allergic Diseases Section studies the mediators and biochemical pathways which underlie allergic reactions. Histamine has been shown to be selectively chemotactic for human eosinophils between 30 and 200 ng/ml histamine. Above 200 ng/ml, histamine progressively diminishes eosinophil responsiveness to histamine and other chemotactic factors such as C5a or kallikrein which is reversible by H2 receptor antagonists but not H1 receptor antagonists. The histamine chemotactic activity is not inhibited by H1 or H2 receptor antagonists. In vivo histamine release has been demonstrated in patients with cold urticaria, cholinergic urticaria, and familial vibratory angioedema. Histamine release with cold exposure is rapid in patients with cold urticaria within 2 minutes after exposure and peaks at 5 minutes. Plasma histamine reached above 100 ng/ml in one patient with hypotension. Histamine release in vibratory angioedema is even more rapid and peaks between 2-3 min. Histamine release in cholinergic urticaria is slow, by comparison, and remains elevated for over 30 minutes after exercise challenge. A new factor required for the normal functioning of the Hageman factor dependent pathways has been identified. A patient, Ms. Williams, was found to possess no detectable kininogen; however, besides the expected inability to generate bradykinin, Hageman factor dependent coagulation and fibrinolysis were markedly impaired. A high molecular weight form of kininogen has been identified as the factor which corrects all of the abnormalities of this plasma and precedes the feedback effects of kallikrein and plasmin upon Hageman factor.